Method and apparatus for visual characterization of tissue
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Abstract
A method for visual characterization of human or animal tissue formed from cells, having the following steps: a radiation source for emitting directional electromagnetic radiation is provided; —the tissue to be irradiated with the radiation, this producing a reflection in the tissue which is characteristic of the tissue, with—the radiation which has penetrated the tissue having, within an excitation region extending transversely with respect to the direction of propagation of the radiation, a sufficient intensity to excite a reflection in the tissue. The radiation emitted by the radiation source is impressed with an intensity profile, transversely with respect to its direction of propagation, which is such that the excitation region covers a plurality of cells of the tissue and the excited reflection originates from inter-cell tissue properties. The invention relates to a method in which the radiation emitted by the radiation source is periodically deflected transversely with respect to the direction of propagation such that the radiation periodically scans a region of the tissue around the measurement point which extends over a plurality of cells of the tissue. The invention also relates to apparatuses for carrying out the methods.
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Citations
132 Claims
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1-66. -66. (canceled)
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67. A method for visual characterization of human or animal tissue formed from cells, comprising the following steps:
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providing a radiation source for emitting directional electromagnetic radiation; and irradiating the tissue to be characterized with the radiation, whereby a reflection radiation which is characteristic of the tissue is generated in the tissue, wherein the radiation that has penetrated into the tissue has, within an excitation region extending transversely with respect to the propagation direction of said radiation, a sufficient intensity to excite a characteristic reflection radiation in the tissue, wherein the radiation emitted by the radiation source has impressed on it an intensity profile transversely with respect to its propagation direction, said intensity profile being such that the excitation region covers a plurality of cells of the tissue and the excited reflection radiation originates from inter-cell tissue properties, wherein impressing the intensity profile is effected by the radiation emitted by the radiation source being split into at least two partial beams, wherein the excitation region is defined by the position of the partial beams. - View Dependent Claims (68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95)
b) in each case the interference detector compares the intensities at adjacent locations with one another in order to determine a location-dependent contrast value; and c) the interference detector determines from location-dependent contrast values an average value representing a characteristic integral contrast variable for the radiation arriving at the detector; d) wherein the impressed intensity profile is detected by the integral contrast variable attaining a maximum.
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80. The method according to claim 78, wherein
a) the interference detector determines the intensity of the radiation arriving at it in a spatially resolved manner in a detection plane perpendicular to the radiation; -
b) a correlation value is determined from the intensity values determined and the intensity profile impressed onto the radiation of the radiation source; c) the impressed intensity profile is detected by the correlation value attending a maximum.
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81. The method according to claim 67, wherein the radiation emitted by the radiation source is deflected transversely with respect to its propagation direction such that a region of the tissue extending parallel to the tissue surface is scanned.
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82. The method according to claim 67, wherein focusing of the radiation emitted by the radiation source into a focal plane is effected in a temporally dependent manner, such that the focal plane is displaced in the propagation direction of the radiation, whereby a region extending perpendicular to the tissue surface is scanned.
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83. The method according to claim 67, wherein the backscattered radiation excited in the tissue is detected in a detector, its intensity being determined in a manner dependent on wavelength and/or time.
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84. The method according to claim 67, wherein
a) the tissue is irradiated with radiation in the wavelength range of 720-800 nm, whereby a two-photon fluorescence is excited in the tissue; -
b) the intensity of a first fluorescence signal at a wavelength of 460±
30 nm and of a second fluorescence signal at a wavelength of 550±
30 nm is detected;c) the ratio of the intensities of the first and second fluorescence signals is determined; and d) a signal is generated in a manner dependent on the ratio determined in step c).
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85. The method according to claim 67, wherein
a) the tissue is irradiated with radiation in the wavelength range between 500-550 nm; -
b) a first intensity of a two-photon fluorescence is detected at a wavelength of 340±
40 nm;c) the tissue is irradiated with radiation in the wavelength range between 720-800 nm; d) a second intensity of a two-photon fluorescence is detected at a wavelength of 460±
40 nm;e) the ratio of the first intensity determined in step b) and the second intensity determined in step d) is determined; and f) a signal is generated in a manner dependent on the ratio determined in step e).
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86. The method according to claim 67, wherein
a) the tissue is irradiated with radiation in the wavelength range between 720-800 nm, and b) an intensity of a two-photon fluorescence is detected at a wavelength of 460± - 40 nm.
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87. The method according to claim 86, wherein the radiation is imaged into the tissue via a lens and the lens is displaced step by step along the propagation direction of the radiation emitted by the radiation source, steps a) and b) being effected for a plurality of lens positions, such that the focus is led in the propagation direction of the radiation through the tissue and fluorescence signal is determined for a plurality of tissue depths.
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88. The method according to claim 87, wherein the method is carried out on a healthy tissue and the intensities of the fluorescence signal that are thus determined are stored as reference values.
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89. The method according to claim 87 wherein
c) the method is carried out in accordance with claim 87 on a tissue to be characterized; -
d) the intensities determined for each depth are related to the respective intensities of the stored reference signal by a ratio; and e) a signal is generated in a manner dependent on the ratio determined in step d).
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90. The method according to claim 89, wherein the signal is generated if the ratio determined in step d) deviates approximately 30% from the value 1.
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91. The method according to claim 67, wherein
a) the tissue is irradiated with a short-pulse laser beam in the wavelength range of 720-880 nm or 980-1080 nm; - and
b) the intensity of returning radiation at half the wavelength of the radiation used for irradiating the tissue in accordance with step a) is detected.
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92. The method according to claim 91, wherein the radiation is imaged into the tissue via a lens and the lens is displaced step by step along the propagation direction of the radiation emitted by the radiation source, steps a) and b) being effected for a plurality of lens positions, such that the focus is led in the propagation direction of the radiation through the tissue and a fluorescence signal is determined for a plurality of tissue depths.
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93. The method according to claim 92, wherein the method is carried out on a healthy tissue and the intensities of the fluorescence signal that are thus determined are stored as reference values.
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94. The method according to claim 92, wherein:
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c) the method is carried out in accordance with claim 91 on a tissue to be characterized, d) the intensities determined for each depth are related to the respective intensities of the stored reference signal by a ratio; and e) a signal is generated in a manner dependent on the ratio determined in step d).
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95. The method according to claim 94, wherein the signal is generated if the ratio determined in step d) deviates approximately 40% from the value 1.
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96. A method for visual characterization of tissue formed from cells, comprising the following steps:
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providing a radiation source for emitting directional radiation; and irradiating the tissue to be characterized with the radiation at a measurement location, whereby a backscattered radiation which is characteristic of the tissue is excited in the tissue, wherein the radiation emitted by the radiation source is periodically deflected transversely with respect to the propagation direction in such a way that the radiation periodically excites a region of the tissue around the measurement location which extends over a plurality of cells of the tissue. - View Dependent Claims (97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110)
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111. An apparatus for characterizing tissue, comprising:
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a radiation source for emitting directional radiation for irradiating the tissue to be characterized, which can excite in the tissue a backscattered radiation which is characteristic of the tissue, radiation that has penetrated into the tissue having, within an excitation region extending transversely with respect to the propagation direction of said radiation, a sufficient intensity to excite a characteristic backscattered radiation in the tissue, and beam shaping means with which the radiation emitted by the radiation source can have impressed on it an intensity profile such that the excitation region can cover a plurality of cells of the tissue and the backscattered radiation excited upon the irradiation of the tissue originates from inter-cell tissue properties, wherein the beam shaping means are designed to split the radiation emitted by the radiation source into at least two partial beams. - View Dependent Claims (112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124)
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- 125. An apparatus for characterizing tissue, comprising a radiation source for generating directional radiation for irradiating the tissue to be characterized and deflection means for deflecting radiation generated by the radiation source, by which the radiation can be periodically deflected transversely with respect to the propagation direction, such that the radiation can periodically excite a region of the tissue around a measurement location extending over a plurality of cells of the tissue.
Specification